Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.

Protection Efficacy of Recombinant Infectious Laryngotracheitis Vaccine in Chicks

A commercial recombinant fowl pox vectored infectious laryngotracheitis （ILT） vaccine was examined its protection efficacy in one-day-old chicks by subcutaneous route with various dose-strength. The treatment groups I-III birds were vaccinated with a full, 1/2 and 1/3 dose of recommendation dose, respectively. Thereafter, at 6 wk post vaccination, they were challenged with 5x labeled dose of live ILT vaccine. Protection efficacy of the vaccine was compared among groups based on antibody production and eye lesion score. The results of eye lesion score showed that there was a significant difference between control and treatment groups, whereas the difference was not found among the treatment groups. For seroconversion, there was no significant difference between birds in group I and II. However, higher number of seroconversion birds in groups I and II than group III was observed （P 〈 0.05）. It was concluded that a half dose of recommendation dose had the same protection efficacy as a full dose of recombinant YP-LT vaccine.